Evaluation of the effects of vitamin D analogs, bevacizumab, and radiotherapy in uveal melanoma cells.

Due to the lack of a definitive effective treatment method that provides a complete cure and increases survival rates in uveal melanoma, the search for alternative treatments at the molecular level continues. In this context, we aimed to comparatively analyze the therapeutic effects of 25-hydroxyvitamin D3 (D2), 1a, 25-dihydroxyvitamin D3 (D3), bevacizumab and radiotherapy (RT) in a uveal melanoma cell line (MP41). Cytotoxicity was evaluated using XTT cell proliferation kit and Xcelligence cell analyzer system. RT dose was determined after a clonogenic assay. Annexin V/PI staining and Western blot analyses for caspase-3, -8, and -9 were performed to analyze apoptosis. Additionally, cell cycle analyses were also conducted. As a result, we found that D2 and D3 did not show cytotoxic effects, while bevacizumab and RT showed time and dose-dependent cytotoxicity. IC50 concentration of bevacizumab was 6.945 mg/mL. Radiotherapy and bevacizumab significantly reduced cell survival and induced apoptosis when administered both as monotherapy and in combination. A significant increase in caspase proteins was detected at high bevacizumab concentrations. However, the combination of bevacizumab and radiotherapy caused a substantial decrease in caspase-3, -8 and -9 expressions. No significant difference in cell cycle distribution was detected in any treatment. Our results showed that bevacizumab inhibited MP41 cell proliferation and had an additive effect when administered with RT. In conclusion, our study offers a different perspective on the treatment of uveal melanoma, and these results, when supported by animal experiments and clinical studies in the future, might be a new step in the treatment of this challenging ocular tumor.

Thrombotic Microangiopathy Following Hematopoietic Stem Cell Transplantation: A Case of Purtscher-like Retinopathy.

Purtscher-like retinopathy (PLR) is a rare entity related with retinal ischemia due to endothelial dysfunction and embolization. We present a case of a 17-year-old patient who presented with PLR associated with transplant-associated thrombotic microangiopathy. Visual acuity was finger counting at 1 meter in both eyes. Fundoscopy demonstrated peripapillary cotton-wool spots and hypopigmentation in the middle peripheral retina. Both eyes showed signs of macular edema with intraretinal hemorrhages. Optical coherence tomography and fundus fluorescence angiography was performed to support the diagnosis. After systemic treatments and panretinal photocoagulation, the patient's vision improved and the macular edema resolved. [Ophthalmic Surg Lasers Imaging Retina 2024;55:XX-XX.].

Impression Cytologic Evaluation of the Conjunctiva in Patients Treated with Topical 1% Voriconazole

Objectives: The aim of the present study was to evaluate any conjunctival metaplastic changes by impression cytology in patients who underwent topical 1% voriconazole treatment for severe fungal keratitis. Materials and Methods: The study was conducted at Ege University Faculty of Medicine, Departments of Ophthalmology and Medical Pathology. Patients who were treated with 1% topical voriconazole for fungal keratitis for at least 3 months were included. The used topical voriconazole treatment was initiated as one drop every hour and was tapered according to clinical improvement in all patients. Treatment was continued 4 times a day for at least 3 months. Impression cytology samples were collected at least 3 months after cessation of topical voriconazole from the affected eyes and from the fellow eyes as a control group. Collected specimens were transferred to the pathology department for evaluation and grading (Nelson's grading system). Results: The mean age of the patients was 57.68±17.32 years (range, 22-87 years). The impression cytology grade of the inferior bulbar conjunctiva was 1.73±0.77 (range, 0-3) in the study group and 1.19±0.98 (range, 0-3) in the control group (p=0.03). The impression cytology grade of the temporal bulbar conjunctiva was 1.69±0.73 (range, 0-3) in the study group and 1.15±0.88 (range, 0-3) in the control group (p=0.02). The impression cytology grades of the nasal and superior bulbar conjunctiva did not differ statistically (p values 0.13 and 0.17, respectively). Conclusion: Topical voriconazole is an effective broad-spectrum antifungal drug, but it induces conjunctival squamous metaplasia. Clinicians should be aware of this possible side effect of topical voriconazole and should carefully evaluate the conjunctiva of treated patients at each visit to detect possible metaplastic changes.

Comparison of Optical Coherence Tomography Angiography Findings between Healthy Children and Children with Type 1 Diabetes Mellitus and Autoimmune Thyroiditis

Objective: The aim of this study was to compare the development of early diabetic retinopathy (DR) findings, a microvascular complication, between patients with isolated type 1 diabetes mellitus (T1DM) (Group 1), concurrent T1DM and autoimmune thyroiditis (AT) (Group 2), and healthy controls (Group 3), who were matched for age, sex, number, and body mass index for comparison. Methods: This was a prospective observational study that included individuals aged 10-20 years, and patients in Groups 1 and 2 had been followed up for ≥5 years. None of them developed clinical DR during the follow-up period. Optical coherence tomography angiography (OCTA) was used to evaluate the foveal avascular zone (FAZ) and parafoveal vascular density (PVD) for the development of early DR. OCTA findings were compared between patients and healthy controls. Results: Thirty-five individuals were included in each of the groups. The mean FAZ and PVD differed significantly between the three groups (FAZ, p=0.016; PVD, p=0.006). The mean FAZ was higher in Groups 1 and 2 than in Group 3 (p=0.013 and p=0.119, respectively). The mean PVD was lower in Groups 1 and 2 than in Group 3 (p=0.007, respectively). No significant difference was found between Groups 1 and 2 in terms of the mean FAZ and PVD (p=0.832 and p=0.653, respectively). The mean glycated hemoglobin (HbA1c) level was significantly correlated with FAZ and PVD (FAZ: r=0.496, p<0.001; PVD: r=-0.36, p=0.001). Conclusion: In patients with T1DM who did not develop clinical DR, OCTA findings revealed an increase in FAZ, which was associated with higher HbA1c levels. The mean PVD was significantly lower in the group with coexisting AT and T1DM than in the control group. These results suggest that the coexistence of AT and T1DM can contribute to the development of microvascular complications. However, studies with larger patient series are required.

Optic Capture Without Anterior Vitrectomy in Pediatric Cataract Surgery.

PURPOSE: To compare outcomes of 2 surgical techniques in children undergoing cataract surgery with intraocular lens (IOL) implantation: optic capture of IOL without anterior vitrectomy (AV) or in-the-bag IOL with AV. DESIGN: Prospective randomized controlled trial. METHODS: Patients were randomized to 2 groups: optic capture without AV (group 1) or in-the-bag implantation with AV (group 2). The following variables were compared: visual axis opacification (VAO), inflammatory deposits on IOL surface, anteroposterior synechia, IOL tilt and decentration, lenticular astigmatism, refractive prediction error, and posterior segment complications. RESULTS: Fifty-one eyes of 37 children were investigated with a mean follow-up of 20.1±8.5 months. Group 1 and group 2 had mean ages of 59.2±32.6 and 46.5±21.9 months, respectively (P = .104). Three eyes in group 1 and 2 eyes in group 2 developed VAO (P = .656). Two eyes in group 1 and 5 eyes in group 2 developed anteroposterior synechia (P = .291). Six eyes in group 1 and 11 eyes in group 2 had inflammatory deposits on the IOL (P = .233). Both groups had similar IOL tilt and decentralization (for all meridians, P > .05). The absolute refractive prediction error was 0.55±0.34 diopter (D) and 0.53±0.3 D, respectively (P = .294). Each group had 1 eye with intraocular hypertension (P = .932). CONCLUSION: The optic capture method was similar to the conventional technique in the quantitative evaluation of comprehensive data such as visual axis opacification, inflammatory sequelae, refractive outcomes, and IOL stability. The optic capture technique is an appealing option for pediatric cataract surgery because it eliminates the requirement for vitrectomy.

Multimodal Imaging of Pigmented Paravenous Retinochoroidal Atrophy in a Pediatric Patient with Cystoid Macular Edema.

The aim of this case report is to present the multimodal imaging characteristics of pigmented paravenous retinochoroidal atrophy (PPRCA) in a pediatric patient with cystoid macular edema (CME). A 7-year-old girl was admitted to our clinic with complaints of mild blurred vision and poor night vision. Best corrected visual acuity was 10/10 in both eyes. Fundus examination showed atrophic areas around the optic nerve and along the retinal vessels in both eyes. A few small dot-shaped paravenous pigmentations were observed in the mid-peripheral retina. Fundus autofluorescence was consistent with PPRCA. Spectral-domain optical coherence tomography (OCT) revealed the presence of CME and loss of the outer retinal layers outside the macula, with intact retinal layers in the macula. OCT angiography revealed normal choriocapillaris vasculature and flow. The patient was followed up for 6 months but showed no change in CME or clinical appearance. CME without ocular inflammation is an unusual finding of PPRCA and may suggest the involvement of chronic or latent inflammation in the etiology of PPRCA.

Correction of high astigmatism with toric intraocular lens in eyes with corneal transplant.

OBJECTIVES: To evaluate the results of toric intraocular lens (IOL) implantation during cataract surgery in eyes with high regular astigmatism associated with prior penetrating keratoplasty (PK). METHODS: A retrospective data analysis of patients with prior PK, who underwent uncomplicated cataract surgery with hydrophobic toric single piece IOL (EyeCryl Toric®, Biotech Vision Care, Luzern, Switzerland). RESULTS: A total of 18 eyes of 18 patients were included in the study. The mean age was 53.4 ± 12.4 (25-70) years. The mean follow-up period was 15.5 (4-24) months. The mean best corrected visual acuity (BCVA) significantly increased from 1.36 ± 1.0 logMAR to 0.31 ± 0.17 logMAR (p < .001) pre- and post-operative 4 weeks, respectively. There was no significant change in mean BCVA during follow-up; mean BCVA was 0.32 ± 0.17 logMAR at the last visit. The mean pre-operative topographic astigmatism was 6.52 ± 1.80 diopters (D). The mean manifest refraction astigmatism was decreased from 6.55 ± 1.62 D to 2.80 ± 1.43 D (p˂0.001). The mean Surgically induced astigmatism (SIA) was 3.74 ± 0.77 D according to vector analysis. There was no patient with graft rejection or failure, the mean endothelial cell loss rate was 12.75 ± 3.76% (7-17%). There was no patient requiring IOL reposition. CONCLUSIONS: Toric IOL implantation during cataract surgery provides an option to correct astigmatism in post-PK eyes with high regular astigmatism. When appropriate patients are selected it is a safe method to achieve significant improvements in visual acuity and astigmatism.

The effect of topical voriconazole on conjunctiva in rats as revealed by histopathology and immunohistochemistry.

The aim of this study was to evaluate the effects of topical voriconazole with histopathological and immunohistochemical analysis of the conjunctiva in rats. Twenty-eight Sprague Dawley rats were divided into four groups as two study (S1, S2) and two control (C1, C2). Voriconazole was instilled four times daily to S1, S2 rats. Physiologic saline (0.9%) was instilled four times daily in C1 and C2 rats. S1 and C1 were followed in a dark room; S2 and C2 were held in a room with sunlight. Impression cytology was performed at 0, 15, 30, 45 and 60th d after instillations. After 2 months of treatment conjunctival tissue was removed for histological and immunohistochemical analysis. In impression cytology evaluation, there was no difference between S1 and S2. At 60 d the difference between S1 and C1 was significant. In other comparisons, there was no difference between S1 and C1, C2. The scores of S2 was higher than C1 and C2 for all comparisons except 15th day scores of S2 and C2. In study groups, epithelial and gland degeneration were higher in S2, but inflammation scores were similar. The comparison of immunreactivity of ERK, TGFß and E-cadherin were different in the study groups than the control groups for all comparisons. In conclusion, voriconazole has side effects due to phototoxicity including squamous cell carcinoma. Clinicians should particularly be careful with the long-term use of topical voriconazole and should follow-up patients strictly in terms of ocular surface alterations.

The Role of Posterior Vitreous Detachment and Vitreomacular Adhesion in Patients With Age-Related Macular Degeneration.

BACKGROUND AND OBJECTIVE: The aim of this study was to assess the prevalence of posterior vitreous detachment (PVD) and vitreoretinal interface in patients with age-related macular degeneration (AMD). PATIENTS AND METHODS: This clinical trial included 206 eyes of 138 patients who presented to the authors' clinic between January 2012 and November 2014. Patients were divided into three groups: 98 eyes of 67 patients with exudative AMD, 55 eyes of 36 patients with nonexudative AMD, and 53 eyes of 35 patients having no vitreoretinal disease. All patients underwent complete ocular examination, including best-corrected visual acuity, Goldmann applanation tonometry, fundus photography, spectral-domain optical coherence tomography, and B-mode ultrasonography at 6 months and 12 months after the initial examination. RESULTS: Total and partial PVD rates were significantly higher at baseline, 6 months, and 12 months in both exudative and nonexudative AMD groups when compared to the control group (Chi-square test, P = .006, P = .001, and P = .009, respectively). The prevalence of total PVD was significantly higher in nonexudative AMD, whereas partial PVD was higher in exudative AMD. The exudative AMD group reported significantly more VMA than the other two groups at baseline, 6 months, and 12 months (Chi-square test, P =.005, P = .003, and P = .019, respectively). CONCLUSION: This study indicates that the incidence of vitreoretinal interface abnormalities such as partial PVD and vitreomacular adhesion were higher in the exudative AMD group. It can be concluded that abnormal adhesive and tractional forces due to PVD may play a role in the progression of AMD. [Ophthalmic Surg Lasers Imaging Retina. 2017;48:223-229.].

Evaluation of posterior vitreous detachment after uneventful phacoemulsification surgery by optical coherence tomography and ultrasonography.

BACKGROUND: The aim was to investigate the effect of uneventful phacoemulsification on vitreoretinal interface evaluated by optical coherence tomography (OCT) and ultrasound. METHODS: One hundred and fifty eyes were evaluated for the presence or absence of posterior vitreous detachment by ultrasound and OCT prior to cataract surgery. Only those eyes with intact vitreoretinal adhesion were included in the study. All patients underwent cataract surgery. At one month, three months and six months, all patients were assessed with OCT and ultrasound. The data were analysed for statistical significance. RESULTS: The study was carried out on 30 of 31 patients with no posterior vitreous detachment. The mean age of patients was 62.63 ± 7.15 years (range 49 to 75 years) and 15 were female. Posterior vitreous detachment developed in 17 patients (56.66 per cent) at one month, 21 patients (70 per cent) at three months and 22 patients (73.33 per cent) at six months following the surgery. No complications or acute symptoms were detected associated with posterior vitreous detachment. CONCLUSION: Vitreoretinal interface changes and vitreoretinal separations and progression of separation can be easily evaluated by OCT. The current study confirms that posterior vitreous detachment occurs commonly soon after cataract surgery.

Ocular response analyser measurements and central corneal thickness in ocular rosacea patients.

Rosacea is a chronic cutaneous disorder which is known to cause inflammation and increased proteolytic activity on the ocular surface that might lead to corneal biomechanical alterations. The aim of this study is to evaluate the corneal biomechanical properties of ocular rosacea patients and compare the measurements with healthy individuals as measured with Reichert ocular response analyser (ORA). Besides full eye examination [best corrected visual acuity (BCVA), intraocular pressure (IOP) measured with Goldmann applanation tonometry (IOP-G)], central corneal thickness (CCT), and ORA [corneal hysteresis (CH), corneal resistance factor (CRF), corneal compensated IOP (IOPcc), Goldmann correlated IOP (IOPg)] measurements of 30 eyes of 15 ocular rosacea patients (study group) and 30 eyes of 15 healthy individuals (control group) were performed. For comparisons paired t test was used. Mean age of study group was 45.26 ± 11.65 (range 25 and 63) and control group was 45.00 ± 8.91 (range 26 and 58) years (p = 0.865). No significant difference in BCVA, CCT, IOP-G, IOPcc was detected among groups. However, IOPg, CH, and CRF in the study group were significantly lower than in the control group (p = 0.013, p = 0.013, p = 0.009, respectively). IOPg, CH, and CRF parameters of ocular rosacea patients were significantly lower than normal individuals. These differences and their probable clinical reflections that might effect making decisions in conditions such as glaucoma should be investigated in larger number of patients.

Evaluation of Ex-PRESS mini glaucoma shunt implantation with preoperative intracameral bevacizumab injection in refractory neovascular glaucoma.

PURPOSE: To evaluate the efficacy and safety of Ex-PRESS mini glaucoma shunt implantation with preoperative intracameral bevacizumab injection in eyes with refractory neovascular glaucoma. METHODS: A retrospective chart review of patients with medically uncontrolled neovascular glaucoma who had received 50-µL intracameral bevacizumab (1.25 mg) before undergoing Ex-PRESS mini glaucoma shunt implantation was performed. Success was defined as a postoperative intraocular pressure (IOP) between 5 and 21 mm Hg without (complete success) or with or without (qualified success) glaucoma medications and no additional glaucoma surgery, or loss of light perception. RESULTS: In total, 33 eyes of 33 patients (15 female, 18 male) were enrolled in the study. The mean age of the study population was 61.2 years (range 36-78). The mean IOP decreased from 41.0 mm Hg (range 24-72) to 17.6 mm Hg (range 8-28) over a mean follow-up of 20.9 months (range 6-60) (p<0.001; Wilcoxon signed-rank test). Complete and qualified success rates were 36.4% and 66.7%, respectively. The average number of antiglaucoma medications decreased from 3.5 (range 2-4) preoperatively to 1.8 (range 1-4) postoperatively (p<0.001; Wilcoxon signed rank test). In 81.8% of cases, the decrease in IOP was 30% or more postoperatively. CONCLUSIONS: Ex-PRESS mini glaucoma shunt implantation with preoperative bevacizumab injection may be an effective alternative procedure for refractory neovascular glaucoma.

Evaluation of Filtering Bleb Function after Trabeculectomy with Mitomycin C Using Biomicroscopy, Anterior Segment Optical Coherence Tomography and In Vivo Confocal Microscopy.

OBJECTIVES: To analyze and assess compatibility of trabeculectomy filtering bleb characteristics and appearances using biomicroscopy, anterior segment optical coherence tomography (AS-OCT) and in vivo confocal microscopy (IVCM). MATERIALS AND METHODS: Twenty-eight eyes of 28 patients who underwent glaucoma filtering surgery with mitomycin C in our clinic between 2009 and 2013 were evaluated. Morphological appearances of the blebs on slit-lamp biomicroscopy were defined according to the Moorfields bleb classification system. For the internal tissue assessment of blebs, AS-OCT and IVCM were performed. Bleb biometric parameters such as length, height and bleb wall thickness were assessed by AS-OCT; conjunctival epithelial-stromal cyst, structural network of conjunctival stroma and vascularisation were examined with IVCM. The relation between biomicroscopic morphological staging and bleb characteristics detected on AS-OCT and IVCM were assessed. RESULTS: The mean age of the 28 patients (16 male, 12 female) was 57.2±15.9 (19 to 79) years. The mean time elapsed between surgery and examination was 29.2±19.2 (6 to 68) months. According to biomicroscopic appearance, 17 (60.7%) blebs were functional (13 diffuse, 4 microcystic), whereas 11 (39.3%) blebs were non-functional (9 flat, 2 encapsulated). In the comparison of non-functional and functional blebs, functional blebs were found to be superior in terms of biometric parameters on AS-OCT assessment (p<0.05). Higher number of epithelial and stromal cysts and less vascularisation were detected by IVCM in functional blebs when compared with non-functional blebs (p<0.05). CONCLUSION: Biomicroscopic appearances and characteristics on AS-OCT and IVCM of filtration blebs are consistent with each other. Besides biomicroscopic examination, which is an easy and practical method for determining bleb morphology, cross-sectional images obtained by AS-OCT and IVCM provide objective data regarding internal structure and functional features of blebs.

Evaluation of dry eye and meibomian gland dysfunction with meibography in patients with rosacea.

PURPOSE: To evaluate the dry eye tests and meibography of patients with ocular rosacea. METHODS: Thirty-six eyes of 18 patients with ocular rosacea (group 1) and 38 eyes of 19 healthy individuals (group 2) were enrolled. Besides full-eye examination, corneal and conjunctival fluorescein staining and Oxford scoring, tear film break-up time, Schirmer 1 test, ocular surface disease index score assessment, and evaluation of upper and lower eyelid meibomian glands using infrared captures of an optical coherence tomography (OCT) (Spectralis HRA+OCT; Heidelberg Engineering) device were performed (grade 0: no loss of meibomian glands, grade 1: gland dropout area <1/3 of the total meibomian glands, grade 2: gland dropout area 1/3 to 2/3 of the total meibomian glands, grade 3: gland dropout >2/3 of the total meibomian glands). RESULTS: The mean ages of group 1 and group 2 were 50.2 ± 9.5 (range, 32-65), and 46.3 ± 14.1 years (range, 25-70), respectively (P = 0.225). No significant difference in best-corrected visual acuity and meiboscores of upper eyelids were detected in between groups. Schirmer 1 and tear film break-up time in group 1 were significantly lower than in group 2 (P = 0.005, P < 0.001, respectively). Ocular surface disease index and Oxford scale scores and meiboscores of lower and total (upper + lower) eyelids were significantly higher in group 1 than in group 2 (P = 0.04, P = 0.018, P < 0.001, P = 0.03, respectively). CONCLUSIONS: Ocular rosacea causes dry eye and significant meibomian gland loss that can objectively be demonstrated with meibography. The infrared camera of OCT-that is widely found in many ophthalmology departments-might be used to evaluate meibomian gland dysfunction in these individuals.

Posterior segment intraocular foreign bodies: the effect of weight and size, early versus late vitrectomy and outcomes.

BACKGROUND: The objective of this study was to identify the effects of weight and size characteristics of posterior segment intraocular foreign bodies (IOFBs) in open globe injuries. METHODS: Fifty-eight eyes of 58 patients with posterior segment IOFBs were enrolled in the study. All IOFBs were removed by pars plana vitrectomy. Factors including age, gender, best corrected visual acuity (BCVA), nature of IOFBs, weight and dimensions of IOFBs, initial ocular features, timing of IOFB removal, entry site of IOFBs, interventions and complications were evaluated. RESULTS: Mean age of the patients was 32.7±14.2 years, and mean follow up period was 18±13.3 months. Weight, length, width and thickness of IOFBs were found negatively correlated with initial and final BCVA levels (p<0.05). Weight of IOFBs was significantly greater in eyes with initial hyphema, vitreous hemorrhage, retinal hemorrhage, retinal detachment, and uveal prolapse (p<0.05). Width and thickness of IOFBs were significantly greater in eyes with hyphema, vitreous hemorrhage, retinal hemorrhage and uveal prolapse (p<0.05). Length of IOFBs was significantly longer in eyes with hyphema (p<0.05). Presence of initial or subsequent retinal detachment was associated with poor final BCVA (p<0.05). There was no association between the timing of IOFB removal and incidence of endophthalmitis. CONCLUSION: Greater weight and size of posterior segment IOFBs were associated with worse outcomes in open globe injuries. Protective eyewear has a crucial importance to avoid work-related injuries. In our study, early or late vitrectomy for an IOFB removal had no significant effect on anatomic and visual outcomes. Therefore, vitrectomy can be postponed until optimal conditions are obtained.